Apellis Pharmaceuticals Inc (APLS) 2024 Q4 法說會逐字稿

Good morning, ladies and gentlemen. Thank you for standing by, and welcome to the Apellis Pharmaceuticals fourth quarter and full year 2024 earnings conference call. (Operator Instructions) After the speaker's presentation, there will be a question-and-answer session. (Operator Instructions) Please be advised that today's conference is being recorded. I would now like to turn the call over to Meredith Kaya, Senior Vice President, Investor Relations, and Strategic Finance. Please go ahead.

女士們、先生們，早安。感謝您的支持，歡迎參加 Apellis Pharmaceuticals 2024 年第四季和全年財報電話會議。（操作員指示）演講者演講結束後，將有一個問答環節。（操作員指示）請注意，今天的會議正在錄音。現在，我想將電話轉給投資者關係和策略財務高級副總裁 Meredith Kaya。請繼續。

Good morning, and thank you for joining us to discuss the Apellis fourth quarter and full year 2024 financial results. With me on the call are Co-Founder and Chief Executive Officer, Dr. Cedric Francois; Executive Vice President of Commercial, David Acheson; Chief Medical Officer, Dr. Caroline Baumal; and Chief Financial Officer, Tim Sullivan.

早安，感謝您加入我們討論 Apellis 第四季和 2024 年全年財務表現。與我一起參加電話會議的還有共同創辦人兼執行長 Cedric Francois 博士；商務執行副總裁 David Acheson；首席醫療官 Caroline Baumal 博士；和財務長 Tim Sullivan。

Before we begin, let me point out that we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail.

在我們開始之前，請允許我指出，我們將根據我們當前的期望和信念做出前瞻性的陳述。這些聲明受一定風險和不確定性的影響，實際結果可能有重大差異。我鼓勵您查閱我們提交給美國證券交易委員會的文件中討論的風險因素，以獲取更多詳細資訊。

Now I'll turn the call over to Cedric.

現在我將電話轉給塞德里克。

Thank you, Meredith, and thank you all for joining us this morning. As we close out another year, I would like to recognize the progress our team has made. We achieved important milestones in 2024, strengthening our business while navigating some headwinds along the way.

謝謝你，梅雷迪斯，也謝謝大家今天早上加入我們。在新的一年即將結束之際，我想認可我們團隊的進步。我們在 2024 年取得了重要的里程碑，在克服了一些不利因素的同時，也增強了我們的業務。

SYFOVRE generated over 120% year-over-year US net revenue growth. We presented positive Phase III value in data with EMPAVELI C3G and ICF-PGM. We advanced our earlier-stage pipeline and we fortified our financial position.

SYFOVRE 美國淨收入年增超過 120%。我們透過 EMPAVELI C3G 和 ICF-PGM 數據展示了積極的 III 期價值。我們推動了早期階段的研發管線，並鞏固了我們的財務狀況。

Looking ahead, our strategy is focused on three key pillars: first, to transform the treatment of geographic atrophy with SYFOVRE. Second, to maximize EMPAVELI impact in rare diseases. And third, to advance our innovative pipeline, leveraging our expertise in complement site.

展望未來，我們的策略重點集中在三大支柱：首先，利用 SYFOVRE 改變地圖樣萎縮的治療方法。第二，最大限度地發揮EMPAVELI對罕見疾病的影響力。第三，利用我們在補充站點方面的專業知識，推動我們的創新管道。

Starting with (inaudible) number 1, SYFOVRE is the market-leading treatment for geographic atrophy in the US with more than 510,000 injections administered through December. Recent regulatory developments within the competitive landscape confirm our view that SYFOVRE is the leading treatment for GA.

從（聽不清楚）1號開始，SYFOVRE 是美國地圖樣萎縮市場領先的治療方法，截至 12 月已註射超過 51 萬次。競爭環境中的最新監管發展證實了我們的觀點，即 SYFOVRE 是治療 GA 的主要方法。

SYFOVRE's unmatched presubsiding label, which includes increasing effects over time and flexible dosing will enable us to further strengthen SYFOVRE's market leadership over time. SYFOVRE has generated nearly $900 million in sales in less than two years, making this one of the most successful launches in recent history, with only two approved treatment options available. Hence, no new competitors on the horizon, we are in a strong position.

SYFOVRE 無與倫比的預付標籤，包括隨著時間的推移而增加的效果和靈活的劑量，將使我們能夠進一步加強 SYFOVRE 的市場領導地位。SYFOVRE 在不到兩年的時間內創造了近 9 億美元的銷售額，成為近代史上最成功的上市產品之一，目前僅有兩種核准的治療方案可供選擇。因此，由於沒有新的競爭對手，我們處於強勢地位。

Our two key priorities heading into the rest of 2025 are to secure SYFOVRE's leadership and to grow the overall GA market. We are still in the early phases of growth and estimate that only health of diagnosed GA patients are seen by an eyecare professional. Of those less than 10% are receiving treatment.

我們在 2025 年剩餘時間的兩個主要任務是確保 SYFOVRE 的領導地位並發展整個 GA 市場。我們仍處於發展初期，估計只有確診的 GA 患者的健康狀況才能得到眼科保健專業人員的關注。其中，不到10％的人正在接受治療。

Building a new market takes time, but we have the right products, strategy, and team to execute. The US is our primary commercial focus for SYFOVRE, but we will continue to explore select international markets. We were pleased to receive approval from the Therapeutic Goods Administration in Australia last month and our regulatory review in Switzerland is ongoing.

開拓新市場需要時間，但我們有合適的產品、策略和團隊來執行。美國是 SYFOVRE 的主要商業重點，但我們將繼續探索精選的國際市場。我們很高興上個月獲得了澳洲治療用品管理局的批准，我們在瑞士的監管審查正在進行中。

As we continue to focus our efforts on the SYFOVRE launch, we are also working to develop the next-generation treatment for GA. To do this, we are combined SYFOVRE and APL-3007 siRNA. This approach is designed to comprehensively block complement activity at the retina as well as the choroid through local and systemic C3 inhibition. We plan to initiate a Phase II trial in the second quarter.

在我們繼續專注於推出 SYFOVRE 的同時，我們也致力於開發下一代 GA 治療方法。為此，我們結合了 SYFOVRE 和 APL-3007 siRNA。此方法旨在透過局部和全身 C3 抑制全面阻斷視網膜和脈絡膜的補體活性。我們計劃在第二季啟動第二階段試驗。

Shifting gears then to our second pillar. Maximizing the impact of EMPAVELI in rare diseases. EMPAVELI continues to elevate the standard of care in PNH. We also look forward to becoming a theater in nephrology starting with the anticipated launch of EMPAVELI in C3G and primary [PACFPGN].

接下來我們討論第二個支柱。最大限度地發揮 EMPAVELI 在罕見疾病方面的作用。EMPAVELI 繼續提高 PNH 的護理標準。我們也期待成為腎臟病學領域的一個舞台，首先是預期在 C3G 和主要地區推出 EMPAVELI[太平洋標準時間]。

We recently filed the supplemental NDA for EMPAVELI based on the positive Phase III valued data. These results hit the trifecta with unprecedented reductions in proteinuria, significant clearance of C3 deposits and stabilization of eGFR. Even more compelling was that these results were consistent regardless of disease types, transplant status or age. If approved, we expect to launch in the second half of 2025.

我們最近根據第三階段的積極價值數據為 EMPAVELI 提交了補充保密申請 (NDA)。這些結果實現了三重效果：蛋白尿得到前所未有的減少、C3 沉積物得到顯著清除以及 eGFR 趨於穩定。更引人注目的是，無論疾病類型、移植狀況或年齡如何，這些結果都是一致的。如果獲得批准，我們預計將於 2025 年下半年推出。

Our partner, Sobi recently received validation of its application, putting them on the closer to making this life-changing treatment available to patients in the [EU]. The second half of 2025, we are also planning to initiate Phase III trials for EMPAVELI in 2 immunonephrology indications, focal segment to glomerulosclerosis and late raft function.

我們的合作夥伴 Sobi 最近獲得了其應用的驗證，這使他們更接近讓這種改變生活的治療方法惠及[歐盟]。2025 年下半年，我們也計劃啟動 EMPAVELI 在 2 種免疫腎病學適應症（局部節段性腎小球硬化和晚期筏功能）中的 III 期試驗。

Lastly, our third pillar, our innovative pipeline. We are excited to be advancing the first ever gene editing approach, targeting the neonatal Fc gamma receptor with our partner being therapeutics. We look forward to sharing more about this program and our broader emerging pipeline with all of you soon. We are excited about the future of Apellis.

最後，我們的第三個支柱是我們的創新管道。我們很高興能夠與我們的合作夥伴一起推進有史以來第一個基因編輯方法，以新生兒 Fc 伽馬受體為目標。我們期待很快與大家分享更多有關該計劃以及我們更廣泛的新興管道的資訊。我們對 Apellis 的未來充滿期待。

We have two potential blockbuster products with SYFOVRE and EMPAVELI, a robust development pipeline of clinical and preclinical programs and a clear path to profitability. I will now turn the call over to David Acheson, our new Executive Vice President of Commercial. I'm sure many of you are familiar with David from previous earnings calls at the investor events, and we are thrilled that he is now using our commercial organization. David?

我們擁有兩款潛在的重磅產品：SYFOVRE 和 EMPAVELI、強大的臨床和臨床前專案開發管道以及明確的獲利途徑。現在我將電話轉給我們新任商業執行副總裁戴維‧艾奇遜 (David Acheson)。我相信你們中的許多人都從以前的投資者活動財報電話會議上熟悉大衛，我們很高興他現在正在使用我們的商業組織。戴維？

Thank you, Cedric, and good morning, everyone. Let me start with SYFOVRE. With over 500,000 injections administered and nearly $900 million in net sales, SYFOVRE has had a remarkable launch. Our focus going forward is to both strengthen our leadership position and grow the overall market.

謝謝你，塞德里克，大家早安。讓我從 SYFOVRE 開始。SYFOVRE 的上市取得了顯著成績，目前已註射超過 50 萬劑，淨銷售額接近 9 億美元。我們未來的重點是加強我們的領導地位並發展整個市場。

The recent regulatory update from our competitor provides us more confidence than ever in the strength of SYFOVRE's differentiated profile. Three things that now are very clear. SYFOVRE has consistently demonstrated robust and increasing effects over time. SYFOVRE is the only GA product approved for as few as six doses per year and SYFOVRE is the only product in a preferred position with many payers.

我們競爭對手最近的監管更新讓我們對 SYFOVRE 差異化優勢比以往任何時候都更有信心。現在有三件事已經非常清楚了。SYFOVRE 一直表現出強勁且不斷增強的效果。SYFOVRE 是唯一一款每年僅批准使用六劑的 GA 產品，也是唯一一款受到眾多付款人青睞的產品。

In the fourth quarter, SYFOVRE maintained its market leadership with approximately 94,000 doses delivered to physician offices, including 89,000 commercial doses and 4,600 samples. Total market share remained stable at over 60% and new patient share trended positively, ending the year approaching 50%.

第四季度，SYFOVRE 保持了市場領先地位，並向醫生辦公室交付了約 94,000 劑，其中包括 89,000 劑商業劑量和 4,600 個樣本。總市佔率維持穩定在 60% 以上，新患者份額呈正面趨勢，年底接近 50%。

As of December, there are more than 2,300 sites of care that have ordered SYFOVRE. SYFOVRE's fundamentals remained strong. In the first two months of 2025, we are seeing continued growth in the number of SYFOVRE injections administered which is the true measurement of demand. There are, however, a few temporary factors expected to affect orders of commercial vials and net revenue in the first quarter.

截至 12 月，已有超過 2,300 個護理地點訂購了 SYFOVRE。SYFOVRE 的基本面依然強勁。2025 年頭兩個月，我們看到 SYFOVRE 注射數量持續成長，這是需求的真正衡量標準。然而，預計有一些暫時性因素會影響第一季商業小瓶訂單和淨收入。

First, the overall GA market growth in the quarter has been timbered due to typical Q1 dynamics like Medicare reverifications and winter storms affecting distribution and patient visits. And second, we have also seen a spike in sample usage over the past two months. We believe retina specialists are using more samples because of a reported funding gap at non-for-profit co-pay assistant organizations. We estimate there could be 5,000 or more incremental samples used in this quarter as compared to the average quarterly sample volume in 2024.

首先，由於典型的第一季動態，例如醫療保險重新驗證和冬季風暴影響分銷和患者就診，本季整體 GA 市場成長受到抑制。其次，我們也看到過去兩個月樣本使用量激增。我們認為，由於非營利組織共同支付助理組織報告的資金缺口，視網膜專家正在使用更多的樣本。我們估計，與 2024 年的平均季度樣本量相比，本季使用的增量樣本量可能會有 5,000 個或更多。

The momentum we are seeing in injection demand to date sets the stage for continued growth in 2025 and beyond. Maximizing the GA opportunity will require a long-term and strategic approach. We need to make sure each patient has access to a [reta] specialist who can treat them.

我們迄今為止所看到的注射需求動能為 2025 年及以後的持續成長奠定了基礎。最大限度地發揮通用航空的機會需要採取長期且策略性的方法。我們需要確保每位患者都能得到能夠治療他們的專科醫生的治療。

We mean higher utilization from those physicians who are already treating patients with SYFOVRE as well as adoption by retina specialists who may have initially been hesitant to utilize GA treatments. And we must continue to further strengthen our formulary positions, being the only GA products with preferred status provides a significant competitive advantage.

我們的意思是，那些已經使用 SYFOVRE 治療患者的醫生的利用率更高，而那些最初可能不願意使用 GA 治療的視網膜專家的採用率也更高。我們必須繼續進一步加強我們的處方地位，作為唯一具有優先地位的 GA 產品，我們將提供顯著的競爭優勢。

We're executing across key initiatives to achieve these goals, including broadening our reach to the eye care community, amplifying real-world data through key forums, educating payers on SYFOVRE's differentiated value proposition and connected with patients through our DTC campaign.

我們正在執行多項關鍵舉措以實現這些目標，包括擴大我們在眼科護理社區的影響力、透過主要論壇擴大真實世界數據、向付款人介紹 SYFOVRE 的差異化價值主張以及透過我們的 DTC 活動與患者建立聯繫。

We recently launched Phase 2 of our DTC campaign featuring Henry Winkler. This campaign focuses on increasing awareness of GA and SYFOVRE and ensuring GA patients are able to connect to a retina specialist who can treat them.

我們最近啟動了以亨利溫克勒為主角的 DTC 活動的第二階段。這項活動旨在提高人們對 GA 和 SYFOVRE 的認識，並確保 GA 患者能夠聯繫到可以治療他們的視網膜專家。

Now let me shift to EMPAVELI. The commercial medical teams are ramping up their efforts in anticipation of EMPAVELI's potential label expansion into C3G and ICMP later this year. We are in the process of hiring our field-based team which will allow us to hit the ground running and make a significant impact in the early phases of the launch.

現在讓我轉到 EMPAVELI。商業醫療團隊正在加緊努力，以應對 EMPAVELI 今年稍後可能將標籤擴展到 C3G 和 ICMP 的情況。我們正在招募現場團隊，這將使我們能夠立即開始工作並在發布的早期階段發揮重大影響。

Ahead of approval, we are executing several prelaunch activities focusing on disease state awareness. These include participation in key nephrology conferences, building relationships with key physician accounts, KOL and payer engagement and patient education. These activities maximize the likelihood of a successful launch in CG and IC-MPGN.

在獲得批准之前，我們正在執行幾項以疾病狀況意識為重點的發布前活動。這些包括參加主要的腎臟病學會議、與主要醫生建立關係、KOL和付款人參與以及病患教育。這些活動最大限度地提高了 CG 和 IC-MPGN 成功發射的可能性。

They also reinforce our commitment to rare nephrology with our programs in DGF and FSGS. The commercial opportunity is significant with an estimated 5,000 C3G and IC-MPGN patients in the US. EMPAVELI is the only drug to be studied in a broad patient population. Given the strength of the Phase III data, we believe EMPAVELI will be used across all patient groups and disease severity.

他們也透過 DGF 和 FSGS 計畫加強了我們對罕見腎臟病學的承諾。美國約有 5,000 名 C3G 和 IC-MPGN 患者，其商業機會龐大。EMPAVELI 是唯一一種在廣泛患者群體中進行研究的藥物。鑑於第三階段數據的強度，我們相信 EMPAVELI 將適用於所有患者群體和疾病嚴重程度。

Physician feedback has been consistent that treatment choice will be based on efficacy over the route of administration given the severity of C3G and IC-MPGN. Many patients, even those with mild to moderate disease will eventually suffer kidney failure. In PNH, EMPAVELI generated approximately $23 million in US net product revenue in the fourth quarter.

醫師的回饋一致認為，考慮到 C3G 和 IC-MPGN 的嚴重程度，治療選擇將基於療效而不是給藥途徑。許多患者，即使是輕度至中度疾病患者最終也會患有腎衰竭。在 PNH，EMPAVELI 在第四季度創造了約 2,300 萬美元的美國淨產品收入。

Compliance rates remained high at 97%, and the safety profile remains consistent with our previous updates. We expect continued competitive pressure in 2025, but this should be more than offset by initial revenue generated from C3G and IC-MPGN.

合規率仍然高達 97%，且安全狀況與我們先前的更新保持一致。我們預計 2025 年競爭壓力將持續存在，但 C3G 和 IC-MPGN 產生的初始收入應足以抵銷此壓力。

With that, I will now turn the call over to Caroline.

說完這些，我現在將電話轉給卡洛琳。

Thanks, David, and good morning, everyone. I'll start with SYFOVRE. We continue to see evidence supporting SYFOVRE strong efficacy and consistent benefit to GA patients over long periods of time. Earlier this month, we presented 48-month data from our GAIL extension study that reinforce SYFOVRE's increasing effects over time.

謝謝，大衛，大家早安。我將從 SYFOVRE 開始。我們不斷看到證據支持 SYFOVRE 對 GA 患者俱有強大的療效和長期持續的益處。本月早些時候，我們展示了 GAIL 擴展研究的 48 個月數據，這些數據進一步證實了 SYFOVRE 隨著時間的推移而不斷增強的效果。

These data demonstrated that early treatment with SYFOVRE leads to preservation of retina tissue as magnitude of approximately 1.5 disc areas on average at 48 months in non-sepovial-GA patients dosed monthly.

這些數據表明，對於每月服用 SYFOVRE 的非 sepovial-GA 患者，早期治療可在 48 個月時平均保留約 1.5 個視盤區域的視網膜組織。

For context, 1.5 disc areas is the size of approximately 2 Phobia areas, which is considered highly meaningful by retinal specialists. We are also beginning to see real-world evidence of the benefits of SYFOVRE treatment, an independent analysis of real-world data concluded that by month nine of treatment SYFOVRE reduced the annualized growth rate of GA by over 40%.

就上下文而言，1.5 個視盤區域大約相當於 2 個恐懼症區域的大小，視網膜專家認為這具有重要意義。我們也開始看到 SYFOVRE 治療益處的現實證據，對現實數據的獨立分析得出結論，到治療的第九個月，SYFOVRE 將 GA 的年增長率降低了 40% 以上。

Separately, another analysis of real-world data following SYFOVRE treatment showed stable visual acuity over multiple injections. While there are always limitations to independent analyses, these results add to the extensive clinical data set for SYFOVRE and strengthen confidence in its treatment benefit.

另外，另一項對 SYFOVRE 治療後真實世界數據的分析顯示，多次注射後視力保持穩定。雖然獨立分析總是有局限性，但這些結果增加了 SYFOVRE 的大量臨床數據集，並增強了對其治療效果的信心。

As Cedric mentioned, we are also developing a next-generation treatment for GA. We believe combining SYFOVRE and our siRNA APL-3007, may provide comprehensive complement blockade in the retina and in the chloride. Specifically, SYFOVRE inhibits complement in the retina and APL-3007 is intended to target systemic complement activity in the eye. With less C3 present in the eye following administration of APL-3007, there may be an even higher degree of efficacy contribution from SYFOVRE.

正如塞德里克所提到的，我們也在開發下一代 GA 治療方法。我們相信，SYFOVRE 與我們的 siRNA APL-3007 結合，可以為視網膜和氯化物提供全面的補體阻斷。具體來說，SYFOVRE 抑制視網膜中的補體，而 APL-3007 旨在針對眼睛中的全身補體活性。由於使用 APL-3007 後眼 C3 較少，SYFOVRE 的療效貢獻程度可能會更高。

Last month, we shared Phase I data with APL-3007 in healthy volunteers showing greater than 90% knockdown of C3 products as measured by the remaining levels of protein in the blood. We expect to initiate a Phase II study with SYFOVRE and APL-3007 in GA patients in the second quarter.

上個月，我們分享了 APL-3007 在健康志願者身上的 I 期數據，結果顯示透過血液中剩餘的蛋白質水平來衡量，C3 產品的敲除率超過了 90%。我們預計將在第二季度針對 GA 患者啟動 SYFOVRE 和 APL-3007 的 II 期研究。

Shifting to EMPAVELI. The Phase III Valiant results provided further confidence in EMPAVELI's ability to control complement and provide a meaningful difference to patients with rare kidney diseases. Based on these data and the strong rationale for complement inhibition, we plan to initiate two pivotal studies with EMPAVELI in the second half of this year. One in primary focal segmental glomerulosclerosis or FSGS and one in delayed graft function, or DGF.

轉向 EMPAVELI。第三階段 Valiant 的結果進一步增強了人們對 EMPAVELI 控制補體的能力的信心，並為患有罕見腎臟疾病的患者帶來有意義的改變。基於這些數據和補體抑制的強有力理論基礎，我們計劃在今年下半年啟動與 EMPAVELI 的兩個關鍵研究。一種是原發性局部性腎絲球硬化症（FSGS），另一種是移植功能延遲（DGF）。

The complement pathway plays a significant role in both diseases, and there are currently no FDA-approved therapies. FSGS is a rare kidney disease that causes scarring of the glomeruli. Similar to C3G and IC-MPGN, FSGS results in end-stage kidney disease within 5 years to 10 years for approximately half of patients. There are an estimated 13,000 primary FSGS patients in the United States.

補體途徑在這兩種疾病中都發揮著重要作用，目前尚無 FDA 核准的治療方法。FSGS 是一種罕見的腎臟疾病，會導致腎絲球瘢痕形成。與 C3G 和 IC-MPGN 類似，FSGS 會導致約一半的患者在 5 至 10 年內發展為末期腎病。美國估計有 13,000 名原發性 FSGS 患者。

DGF is a complication in kidney transplantation, where the transplant kidney fails to function and typically requires dialysis within the first week of transplant. This negatively affects the long-term survival of the kidney and overall patient outcomes.

DGF 是腎臟移植的併發症，移植的腎臟無法正常運作，通常需要在移植後的第一週內進行透析。這對腎臟的長期存活和患者的整體結果產生負面影響。

In 2023, there were an estimated 21,000 transplants in the US using deceased donor kidney. DGF occurred in 30% to 35% of these transplants. FSGS and DGF were chosen due to their high unmet need, significant complement involvement and our ability to move directly into pivotal programs with potential approvals by 2030.

2023 年，美國估計有 21,000 例使用屍體捐贈腎臟的移植手術。30% 至 35% 的移植患者出現 DGF。之所以選擇 FSGS 和 DGF，是因為它們具有很高的未滿足需求、顯著的補體參與度，而且我們有能力直接進入關鍵項目，並有可能在 2030 年之前獲得批准。

Given our leadership and expertise and complement, we are uniquely positioned to bring treatments to patients with these devastating diseases. I will now turn the call over to Tim for a review of the financials. Tim?

鑑於我們的領導地位、專業知識和補充，我們擁有獨特的優勢，能夠為患有這些毀滅性疾病的患者提供治療。我現在將把電話轉給蒂姆，讓他審查一下財務狀況。提姆？

Thank you, Caroline. I will now provide an overview of our financials. Additional details are available in the press release that we issued earlier this morning. Total revenue for the fourth quarter of 2024 was approximately $213 million including $168 million in SYFOVRE and $23 million in EMPAVELI US net product revenue. Total revenue for the full year 2024 was $781 million, a nearly 100% increase as compared to 2023.

謝謝你，卡洛琳。我現在將概述我們的財務狀況。更多詳細資訊請參閱我們今天早上發布的新聞稿。2024 年第四季的總收入約為 2.13 億美元，其中包括 SYFOVRE 的 1.68 億美元和 EMPAVELI US 淨產品收入 2,300 萬美元。2024 年全年總營收為 7.81 億美元，與 2023 年相比成長近 100%。

Turning to the rest of the P&L. For the fourth quarter, cost of sales was $40.9 million. R&D expenses were $76.4 million. SG&A expenses were $121.5 million, and we reported a net loss of $36.4 million. Regarding SYFOVRE, gross to net remained stable relative to the third quarter. We anticipate gross to net to be in the low to mid-20% range through 2025. We took a 1% price increase on January 1 that is intended to help offset some of the ASP erosion while managing customer reimbursement.

轉向損益表的其餘部分。第四季銷售成本為 4,090 萬美元。研發支出為7,640萬美元。銷售、一般及行政開支支出為 1.215 億美元，淨虧損為 3,640 萬美元。就 SYFOVRE 而言，毛利與淨利比與第三季相比保持穩定。我們預計，到 2025 年，毛利率與淨利率比將處於 20% 至 20% 的中低水準。我們在 1 月 1 日將價格提高了 1%，目的是幫助抵消部分 ASP 的下降，同時管理客戶報銷。

We continue to execute against our strategy while maintaining financial discipline. We made strong progress from a financial perspective in 2024. As you can see on slide 17, our total revenue in 2024 nearly matches our non-GAAP expenditure.

我們將繼續執行我們的策略，同時保持財務紀律。2024 年，我們在財務方面取得了長足的進步。正如您在第 17 張投影片上看到的，我們 2024 年的總收入幾乎與我們的非 GAAP 支出相符。

With $411 million in cash and cash equivalents at the end of 2024, we remain confident in our financial position. We anticipate operating expenses in 2025 to be relatively stable compared to 2024. We expect our existing cash, combined with our future product sales to be sufficient to fund our core business to profitability.

截至 2024 年底，我們的現金和現金等價物為 4.11 億美元，我們對自己的財務狀況仍然充滿信心。我們預計 2025 年的營運費用與 2024 年相比將相對穩定。我們預計，我們現有的現金加上我們未來的產品銷售額足以支持我們的核心業務實現盈利。

Now I hand the call back over to Cedric for closing remarks.

現在我將電話交還給塞德里克，請他作最後發言。

Thanks, Tim. We have started 2025 from a position of strength and are focused on building on the success of SYFOVRE preparing for our second commercial launch with EMPAVELI in C3G and ICM PGN, progressing our pipeline and solidifying our financial position. By doing this, we remain confident in our ability to create significant value for patients and shareholders over the coming years.

謝謝，蒂姆。我們從實力地位開啟了 2025 年，並​​專注於鞏固 SYFOVRE 的成功，為與 EMPAVELI 在 C3G 和 ICM PGN 的第二次商業發布做準備，推進我們的產品線並鞏固我們的財務狀況。透過這樣做，我們對自己在未來幾年為患者和股東創造巨大價值的能力充滿信心。

(Operator Instructions)

（操作員指令）

Jon Miller, Evercore ISI.

喬恩·米勒，Evercore ISI。

Hi, guys. Thanks so much for taking my question and congrats on all the progress. One on EMPAVELI and the kidney indications, I guess, and then a quick follow-up on that. Obviously, your primary endpoint showed really great results with the spot test and UACR but the competitor had a 24-hour endpoint.

嗨，大家好。非常感謝您回答我的問題，並祝賀您取得的所有進展。我想，一個是關於 EMPAVELI 和腎臟適應症，然後對此進行快速跟進。顯然，您的主要終點透過抽樣測試和 UACR 顯示了非常好的結果，但競爭對手的終點是 24 小時。

I know you said in the past that you looked at 24 hours, but we haven't seen it yet. Do you plan on presenting that publicly? I assume it was included in the submission to the FDA. Do you have a sense of which metric the FDA is most focused on? Some commentary on that would be great.

我知道您過去說過您查看了 24 小時，但我們還沒有看到。您打算公開發表這項言論嗎？我認為它已包含在提交給 FDA 的文件中。您是否知道 FDA 最關注哪個指標？對此的一些評論就很好了。

Hi, Jon, thank you so much for that question. So look, we're very excited about the submission with EMPAVELI, of course, and looking forward to feedback in short order. At 24 hours was consistent with what we saw with the spots, but the endpoint, of course, was the spot.

你好，喬恩，非常感謝你提出這個問題。所以，我們當然對 EMPAVELI 的提交感到非常興奮，並期待盡快收到回饋。24 小時時的情況與我們觀察到的斑點一致，但終點當然是斑點。

I think what is really important here is not just the proteinuria, right, but the consistency that we had across all the phenotypes of this disease. And across all of three important metrics that exist. There is, of course, a proteinuria which has such a highly clinically meaningful reduction but we also had to (inaudible) stabilization.

我認為這裡真正重要的不僅僅是蛋白尿，而是我們對這種疾病所有表型的一致性。並涵蓋現有的所有三個重要指標。當然，蛋白尿的減少具有極高的臨床意義，但我們也必須（聽不清楚）穩定下來。

And in addition to that, and I cannot overemphasize that the impressive results on the histopathology, right? I mean, so when you look at these kidneys, you see the C3 deposits go away, melting like snow in the sun, quite frankly, over the course of a couple of months and after six months as much as 70% of patients have no more detectable C3 deposits. So that's something really important in mind, we're excited about the submission about what we can do for patients and the submission of the publication will come out soon as well.

除此之外，我不能過度強調組織病理學上令人印象深刻的結果，對吧？我的意思是，當您觀察這些腎臟時，您會看到 C3 沉積物消失，像陽光下的雪一樣融化，坦白說，在幾個月的時間內，六個月後，多達 70% 的患者不再有可檢測到的 C3 沉積物。所以這是一件非常重要的事情，我們對我們能為患者做些什麼感到很興奮，出版物的提交也將很快出來。

Thank you. Maybe just as a quick follow-up. Given recent news coming out of the agency, I'd love to get a sense of your confidence level that you'll launch in second half of '25 that the agency will be able to meet its PDUFA requirements and you'll get a timely review.

謝謝。或許只是作為一種快速的後續行動。鑑於該機構最近傳出的消息，我很想了解一下您對在25年下半年啟動的該機構是否能夠滿足其PDUFA要求並且您會得到及時審查的信心程度。

Yes. So of course, we have no control of our macro, but at the current point in time, there is no indication at all, but there is any type of dealing.

是的。因此，當然，我們無法控制我們的宏觀，但在當前時間點，沒有任何跡象表明，但存在任何類型的處理。

Thanks so much.

非常感謝。

Tazeen Ahmad, Bank of America Securities.

塔澤恩·艾哈邁德（Tazeen Ahmad），美國銀行證券。

Great. Thank you. Good morning, guys. I have a couple of questions regarding SYFOVRE. So just based on the metrics that you've cited or really trends in the first quarter, how should we be thinking about results in the first quarter relative to 4Q? Could it be that sales would be lower this quarter for the reasons that you mentioned.

偉大的。謝謝。大家早安。我有幾個關於 SYFOVRE 的問題。那麼，僅基於您引用的指標或第一季的實際趨勢，我們應該如何看待第一季相對於第四季的結果？是否由於您提到的原因，本季的銷售額會下降？

And then regarding the beneficial status in Medicare Advantage, do you think that that's going to have an early and noticeable impact on new patient share in the year? Or do you think that's something that would happen more gradually? And then I have a follow-up. Thanks.

然後關於醫療保險優勢計劃的優惠地位，您認為這會對今年的新患者份額產生早期和明顯的影響嗎？或者您認為這是一個會逐漸發生的事情？然後我有一個後續問題。謝謝。

I'm going to hand it over to David.

我要把它交給大衛。

It's David. So like we talked about in the -- in the call, some of the things that we're seeing in Q1 are transit impact to what we think will impact net revenue. And while they are anticipated to be temporary, we do think that Q1 will be lower than Q4 as a result. And we're not going to guide on anything for Q1 beyond that, but that's where we are currently, at least with what we've seen so far.

是大衛。正如我們在電話會議中談到的那樣，我們在第一季看到的一些事情是運輸影響，我們認為這些會影響淨收入。儘管預計這些影響是暫時的，但我們確實認為第一季的業績將低於第四季。我們不會對第一季的其他情況做出任何預測，但這就是我們目前的狀況，至少從目前所看到的情況來看是如此。

It's -- the other thing to note, too, by the way, is one of the things that is really positive for us is that the good news, we're seeing injections, which we talked about in the call as well, grow in Q1 versus Q4 which is very positive for us. And we expect -- once we get some of these temporary impacts against the Q1 numbers out of the way, we should see and continue to see and expect to see 2025 to have growth.

順便說一下，另一件需要注意的事情是，對我們來說真正積極的事情之一是好消息，我們看到注入量（我們在電話會議中也談到了這一點）在第一季度相對於第四季度有所增長，這對我們來說非常積極。我們預計，一旦我們消除第一季數據的一些暫時影響，我們就應該看到並繼續看到 2025 年成長。

Okay. And then my follow-up is about the label change that was made for the competing product. How important is it that the label for IZERVAY will say, monthly injection relative to every other month because it does seem, based on our doc check set up until now, docs seem to have adopted every other month. Do you think that practice will change?

好的。然後我的後續問題是關於競爭產品的標籤變更。IZERVAY 的標籤上寫著相對於每隔一個月注射一次的每月注射，這有多重要，因為根據我們迄今為止設定的文檔檢查，文件似乎已經採用了每隔一個月注射一次。您認為這種做法會改變嗎？

Yes. So look, I think it's a little bit early here, right? In regards to the label change, I think there's still some things here that folks are still trying to figure out. I will tell you myself and Caroline, which I'll hand to in a second for some comment. We were at the Macula Society when this came out, which is a prestigious meeting that was held in Florida.

是的。所以看，我認為現在有點早，對吧？關於標籤的更改，我認為還有一些事情人們仍在試圖弄清楚。我會親自和卡洛琳告訴你，然後我會馬上交給她一些評論。當這個消息公佈時，我們正在參加黃斑學會會議，這是在佛羅裡達州舉行的著名會議。

And the general talk and discussion was around SYFOVRE and the every other month dosing. And I think the more important part was the follow-on to that, which is we had a lot of robust data that was presented at that meeting. That really helped us to solidify even further that SYFOVRE's consistent increase effects over time is going to have impact. And is it have an impact -- that was a lot of the discussion.

一般談話和討論都圍繞著 SYFOVRE 和每隔一個月的劑量進行。我認為更重要的部分是後續行動，即我們在那次會議上展示了大量可靠的數據。這確實幫助我們進一步鞏固了 SYFOVRE 隨著時間的推移而持續增長的效果將會產生影響。它是否會產生影響——這是一個值得討論的問題。

Plus, we're the only product that can be treated, and it's in the label for as few as six doses a year, and we're the only product that has preferred positions with payers. That was the conversation at Macula Society. So I'll hand it over to Caroline for additional comment.

此外，我們是唯一可以治療的產品，標籤上標明每年只需六劑，而且我們是唯一在付款人中享有優先地位的產品。這是黃斑學會 (Macula Society) 的對話。因此我將把它交給 Caroline 來徵求進一步的意見。

Thank you. Hi, Tazeen. What I hear from my colleagues and when I know from being a physician, is that efficacy and convenience are really important driving factors for patients, physicians, and payers. And we have consistently demonstrated efficacy with every other month dosing.

謝謝。你好，Tazeen。我從同事那裡聽到的以及作為醫生所了解到的，功效和便利性對於患者、醫生和付款人來說是真正重要的驅動因素。而且我們已經證明，每隔一個月服藥一次就能取得良好的療效。

This has not been demonstrated with IZERVAY in a clinical trial and the FDA did not approve them for every other month dosing. So our label includes all of our benefits, our efficacy, increasing effect over time and a flexible dosing regimen that includes monthly and every other month dosing.

IZERVAY 的臨床試驗並未證明這一點，且 FDA 未批准每隔一個月服用一次。因此，我們的標籤包含了我們所有的好處、功效、隨時間增加的效果以及靈活的給藥方案，包括每月和每隔一個月的給藥。

Anupam Rama, JPMorgan.

摩根大通的 Anupam Rama。

Hi. Thanks for taking my question. This is actually Malcolm Kuno on for Anupam. So with the IZERVAY headwinds over the last several months and the updated label, what are you hearing from payers on the potential for preferred tiering for SYFOVRE?

你好。感謝您回答我的問題。這實際上是 Malcolm Kuno 為 Anupam 表演的。那麼，鑑於過去幾個月 IZERVAY 的不利因素和更新的標籤，您從付款人那裡聽到了有關 SYFOVRE 優先分級潛力的什麼信息？

Yes, Malcolm, thank you. It's David. Thanks for the question. So we're really fortunate to have a number of payers and sizable plans that have us in a preferred position. I think it's a little hard to forecast what that looks like.

是的，馬爾科姆，謝謝你。是大衛。謝謝你的提問。因此，我們非常幸運，擁有眾多付款人和規模可觀的計劃，使我們處於優先地位。我認為很難預測它會是什麼樣子。

But I will tell you, when we look at and have conversations with the payers, it really comes down to every month dosing and the fact that we have it in the label with the efficacy that matches up to that. So those are the things to keep in mind. And we'll see what happens in the future, but I can't really predict what will happen moving forward with the payers, at least at this point in time.

但我會告訴你，當我們查看並與付款人進行交談時，這實際上歸結為每個月的劑量，以及我們在標籤上註明與之匹配的功效的事實。這些都是需要牢記的事。我們將拭目以待未來會發生什麼，但我真的無法預測付款人未來會發生什麼，至少目前還不能。

Great. Thank you.

偉大的。謝謝。

Salveen Richter, Goldman Sachs.

高盛的薩爾文·里希特（Salveen Richter）。

Good morning. Thanks for taking my question. Could you give us a little bit more color on how we should think about the cadence of the SYFOVRE launch here in 2025, just given the commentary on 1Q being lower than 4Q, but there's growth in 2025. And also in the context of a potential label update for IZERVAY and the formulary status and expansion ex US. Thank you.

早安.感謝您回答我的問題。您能否向我們詳細介紹我們應該如何看待 SYFOVRE 在 2025 年的發布節奏，因為有評論稱第一季度的發布速度低於第四季度，但 2025 年將會增長。此外，還涉及 IZERVAY 的潛在標籤更新以及美國以外的處方狀態和擴展。謝謝。

Thank you, Salveen. So I think, first of all, really important to bear in mind, injections continue to grow, right? And that is a reflection of the unmet need in this disease. Remember, fewer than 10% of patients which geographic (inaudible) has been treated. And only about half of patients are currently being seen by accurate professionals.

謝謝你，薩爾文。因此我認為，首先真正重要的是要記住，注射量會持續增長，對嗎？這反映出這種疾病尚未被滿足的需求。請記住，只有不到 10% 的地理區域（聽不清楚）患者接受了治療。目前只有大約一半的患者得到了精準醫療的診治。

So the opportunity there to do good for patients and to generate revenue is enormous as it has always been. So that is as far as the overall market is concerned. Competitively, quite frankly, I think we are in an enviable position right now. Last year, of course, we went through several motions. But at the end of the day, I think it's important to bear in mind that the CRL for our competitor, beyond whether it's resolved or not now, really called out the shortcomings that our competitor has.

因此，為患者謀福利並創造收入的機會一如既往地巨大。就整個市場而言，這就是情況。坦白說，從競爭角度來看，我認為我們現在處於令人羨慕的地位。當然，去年我們經歷了幾項動議。但最終，我認為重要的是要記住，我們競爭對手的 CRL，無論現在是否得到解決，都真正暴露了我們競爭對手的缺點。

Most notably, the fact that there is that there was a 12-month limitation initially, which a lot of physicians did not know and then, of course, also the lack of data for every other month dosing. So I think it was important to kind of level set the knowledge around two products so that physicians can take the right decisions. So we're very excited about where 2025 is heading and beyond as well.

最值得注意的是，最初存在 12 個月的限制，許多醫生並不知道，當然，也缺乏每隔一個月用藥的數據。因此，我認為對兩種產品的知識進行水平評估非常重要，這樣醫生才能做出正確的決定。因此，我們對 2025 年及以後的發展方向感到非常興奮。

Yigal Nochomovitz, Citigroup.

花旗集團的 Yigal Nochomovitz。

Hey, Cedric and team, thanks for the question. I had a question on the combo trial with OCO 07 and SYFOVRE. How are you thinking about the phasing of the dosing there given the intravitreal and the systemic? Are you going to interweave them? Or can you just talk more about the strategy for that combo dosing? And then will this Phase II have any comparison arm? Or is it just going to be a single arm study? Thank you.

嘿，塞德里克和團隊，謝謝你們提問。我對 OCO 07 和 SYFOVRE 的組合試驗有疑問。考慮到玻璃體內和全身給藥，您如何考慮分階段給藥？你要把它們交織在一起嗎？或者您能否詳細談談該組合劑量的策略？那麼第二階段會有任何對照組嗎？或者這只是一項單臂研究？謝謝。

Thank you so much, Yigal. So we're super excited about our 3007 program, and you are asking, as usual, an excellent question, which is we thought carefully to how to implement this in a physician setting, right? So the idea there is that with a subcutaneous injection, if you lower the systemic levels of C3.

非常感謝，伊加爾。因此，我們對我們的 3007 計劃感到非常興奮，而且您像往常一樣提出了一個很好的問題，即我們是否仔細考慮過如何在醫生環境中實施該計劃，對嗎？因此，如果透過皮下注射降低全身 C3 水平，那麼這個想法就是。

So turning off the faucet, if you want, and you give a strong metric advantage, so dosing advantage to SYFOVRE for, which should still need NDA to control the enzymatic activity of the complement cascade. We will synchronize those injections to every two months and every three month administers, both of which to the intravitreal and the subcutaneous, both of which would happen in the physician's office. So I think that's something really important.

因此，如果您願意，可以關掉水龍頭，這樣您就可以獲得強大的度量優勢，從而為 SYFOVRE 提供劑量優勢，而 SYFOVRE 仍然需要 NDA 來控制補體級聯的酶活性。我們將每兩個月和每三個月同步進行一次注射，兩次注射均為玻璃體內注射和皮下注射，均在醫生辦公室進行。所以我認為這是非常重要的一件事。

There will be a dosing component to this as per usual so that we can explore those two separate posologies. But in the broader strategic context, I mean, we're looking forward to this year to growing the market in GA, truly establishing ourselves as we are the market leader, but growing that share that we have. And then also to what we subjectively, of course, but I believe will be one of the, if not the most exciting developmental program in geographic atrophy by the end of this year and into 2026.

像往常一樣，這將包含一個劑量成分，以便我們可以探索這兩種不同的劑量。但從更廣泛的策略角度來看，我的意思是，我們期待今年在 GA 市場的成長，真正確立我們的市場領導者地位，並擴大我們現有的份額。當然，我們也從主觀角度來看這個問題，但我相信，到今年年底和 2026 年，這將是地理萎縮領域最令人興奮的發展計畫之一。

Thanks. And maybe one for Tim. Just on EMPAVELI. Obviously, you have a ton of really interesting larger indications coming down the pipe, as you've alluded to, the C3G, MPGN, FSGS, potentially DGF. So as far as the patent looks like, do you have any comments on how you might extend that even further given the potential for very significant revenues on these follow-on indications?

謝謝。也許還有一個是給提姆的。就在 EMPAVELI 上。顯然，正如您所提到的，有大量真正有趣的更大跡象即將出現，C3G、MPGN、FSGS，還有可能的DGF。那麼就專利而言，考慮到這些後續適應症可能帶來的非常可觀的收入，您對如何進一步擴大專利範圍有何評論？

Yes, sure. If I heard you correct -- correctly, you asked if there was a way to kind of extend our exclusivity. Is that -- did I understand that perspective?

是的，當然。如果我沒聽錯的話，您問的是是否有辦法延長我們的獨家經營權。那是──我理解了這個觀點嗎？

Yes.

是的。

So we have composition of matter through kind of 20 33-ish in 2035 with customary extensions. So -- that's still a pretty reasonable runway for the indications that we discussed and we discussed that those are both chosen because we believe that we would have the ability to launch those with a significant amount of patent life left.

因此，我們在 2035 年左右透過慣常的延伸來研究物質的組成。所以 - 對於我們討論過的適應症來說，這仍然是一個相當合理的跑道，我們討論過選擇這兩個適應症是因為我們相信我們有能力推出那些還剩有大量專利壽命的適應症。

There are other things that we have in mind. We also have, as Cedric mentioned, some combination product work ongoing that could really change our -- the profile of our systemic administration of -- thanks for the color. So we're looking at life cycle management initiatives as well. But from a composition of matter perspective, 2035 is really where that runs out.

我們還在考慮其他事情。正如塞德里克所提到的，我們還在進行一些組合產品的工作，這些工作可能會真正改變我們的系統管理狀況，感謝您的關注。因此我們也在研究生命週期管理措施。但從物質組成的角度來看，2035 年才是真正結束這一階段的時候。

Okay. That's it. Thank you.

好的。就是這樣。謝謝。

Colleen Kusy, Baird.

科琳·庫西，貝爾德。

Great. Good morning. Thanks for taking our question. Congrats on the progress. So you've had some strong momentum on the payer front last year. Can you put into context what percent of the market you have preferred positioning in? And how much more growth on the payer front do you expect to achieve in 2025?

偉大的。早安.感謝您回答我們的問題。祝賀你取得進展。因此，去年您在付款方面取得了強勁進展。您能否具體說明您在多大比例的市場中處於優先定位？您預計 2025 年付款方方面還將實現多少成長？

Thank you, Colleen. And good to have you back. So I'm going to hand it over to David.

謝謝你，科琳。很高興您回來。所以我要把它交給大衛。

Hey, Colleen, good to hear from you, and thank you for the question. So we've got some big plans like Aetna is a great example that as of January 1 has us in a preferred position and a patient has to start with SYFOVRE before they could move to the competitive product. So there's some big plans that are out there.

嘿，科琳，很高興收到你的來信，謝謝你的提問。因此，我們制定了一些大計劃，例如 Aetna 就是一個很好的例子，從 1 月 1 日起，我們處於優先地位，患者必須先從 SYFOVRE 開始，然後才能轉向競爭產品。因此，我們制定了一些宏偉計劃。

I think percentage-wise, it's a little bit hard to talk through that because there are so many intricacies in the plans on how they actually look at this. And the downstream accounts, in particular, to the PBMs can make their own decisions on what they want to do with that. So -- but I will tell you, we have a number of sizable plans in two major PBMs that have us in a preferred policy position for their downstream accounts to make those decisions on.

我認為從百分比來看，這個問題有點難以討論，因為他們在實際看待這個問題的計劃中存在著許多複雜之處。而下游帳戶，特別是 PBM 帳戶，可以自行決定如何處理這些資金。所以 — — 但我會告訴你，我們在兩個主要的 PBM 中製定了許多規模可觀的計劃，這些計劃使我們處於優先的政策地位，以便他們的下游帳戶做出這些決定。

Great. That's helpful. Thank you. And then for C3G and IC-MPGN, have European regulators and US regulators historically approached that review similarly since we've seen some positive momentum on the European opinion front, just wondering how that decision might have read through to the US review.

偉大的。這很有幫助。謝謝。然後對於 C3G 和 IC-MPGN 來說，歐洲監管機構和美國監管機構歷史上是否也採取過類似的審查方式，因為我們看到歐洲輿論方面出現了一些積極的勢頭，只是想知道這一決定對美國的審查有何影響。

Yes. So thank you so much for that question, Colleen. So our partner, Sobi and Aperia been in lockstep through all of this. And we're very excited about the global deployment of EMPAVELI in the US and Aspaveli US, of course.

是的。非常感謝您提出這個問題，科琳。因此，我們的合作夥伴 Sobi 和 Aperia 在整個過程中始終保持步調一致。當然，我們對 EMPAVELI 在美國和 Aspaveli US 的全球部署感到非常興奮。

I think what's -- and again, kind of highlighting what we've mentioned many times, in the US, for example, we estimate there are approximately 5,000 patients. We estimate and we believe that we will only be competing with the only other product should it be approved and maybe on the market by the time we get there for about 1,000 out of those 5,000.

我認為—再次強調我們多次提到的內容，例如在美國，我們估計大約有 5,000 名患者。我們估計並相信，到那時，我們將只與其他唯一一款產品競爭，一旦獲得批准並可能上市，那麼在這 5,000 種產品中大約有 1,000 種將會被納入其中。

So it's a really special opportunity for us, and the numbers of ours in Europe are quite a bit higher than 5,000, really unique opportunity that deserves the prioritization that it gets within Aeris as well as with our partner, Sobi.

所以這對我們來說是一個非常特殊的機會，我們在歐洲的數量遠遠超過 5,000，這是一個真正獨特的機會，值得在 Aeris 以及我們的合作夥伴 Sobi 中優先考慮。

Great. Thanks for taking our question and congrats on progress.

偉大的。感謝您回答我們的問題，並祝賀您的進展。

Phil Nadeau, TD Cowen.

菲爾·納多（Phil Nadeau），TD Cowen 公司。

Good morning. Thanks for taking our questions. First, a follow-up and another question. The follow-up is on your comments you made about the sampling. Can you go into a little bit more detail on the dynamics of why there's a funding shortage? And what gives you confidence that this is just a Q1 issue and it won't persist later in the year?

早安.感謝您回答我們的問題。首先，我要跟進另一個問題。接下來是您對抽樣的評論。您能否詳細說明資金短缺的動態原因？為什麼您相信這只是第一季的問題，並且不會持續到今年稍後？

Sure. Thank you so much, Phil. So look, the sampling are a reflection of a couple of factors, but one that stands out is what we spoke about before, which are these organizations that provide support to physicians to help with the co-pay of the product. That is not just for SYFOVRE, but for all intravitreal injections. And it's important to note that we do not have real visibility on how this is managed.

當然。非常感謝，菲爾。所以看起來，抽樣反映了幾個因素，但其中一個突出的因素是我們之前談到的，這些組織為醫生提供支持，幫助他們分擔產品的共同支付。這不僅適用於 SYFOVRE，也適用於所有玻璃體內注射。值得注意的是，我們對於如何管理這個問題並沒有真正的了解。

This is by design that is it should be appropriately are independent organizations that determine how they manage their fundings. So we contribute, others contribute. We typically contribute at the beginning of the year, but it can happen throughout the year from other organizations and it has happened before that they run out.

這是設計使然，即它應該由獨立的組織來適當決定如何管理他們的資金。因此我們貢獻，其他人也貢獻。我們通常在年初捐款，但其他組織也可能全年捐款，而且以前也發生過捐款用完的情況。

So what tend to happens is that physicians will go towards sampling to be able to still take care of those patients, right? So I would say that the increase in samples is a reflection of the fact that -- these patients are in need. There is a, hopefully, and final expectations temporary funding gap, the physicians compensate for that, with something.

所以通常會發生的情況是，醫生會去進行採樣以便仍然能夠照顧這些病人，對嗎？所以我想說樣本的增加反映了這些病人有需要。希望和最終期望存在暫時的資金缺口，醫生可以用某種方式來彌補。

Got it. That is helpful. And then part of a question on EMPAVELI, C3G and IC-MPGN. In the slide deck, you outlined four buckets of patients with that disease. Can you talk about how you're going to focus your marketing? For example, will you focus on post-transplant patients where you're likely to be the only option or are there other elements or physicians that you think are our highest priority?

知道了。這很有幫助。然後是關於 EMPAVELI、C3G 和 IC-MPGN 的部分問題。在幻燈片中，您概述了患有該疾病的四類患者。您能談談您將如何專注於您的行銷嗎？例如，您是否會專注於移植後患者，而您可能是唯一的選擇，或者您認為其他因素或醫生是我們最優先考慮的？

Yes. Well, thank you very much, Phil. So again, I think you point on something that we're particularly proud of, which is that when we study these diseases we went very broad, right, we said we're going to study C3G as well as ICGN, which are split about 50-50 in the population that we are targeting.

是的。好吧，非常感謝，菲爾。所以，我認為你再次指出了我們特別引以為豪的一點，那就是當我們研究這些疾病時，我們的範圍非常廣泛，對吧，我們說我們將研究 C3G 和 ICGN，它們在我們目標人群中的比例約為 50-50。

We looked at pre transplant, but also post-transplant, which is a segment that often gets neglected. We studied pediatric patients as well as adults and we studied what happens in this disease is sometimes C3 is depleted. Sometimes it's not we studied everything. And everywhere we saw a consistent response as far as the impact on the disease was concerned. So what that means moving forward because I think what you're asking is where is kind of the -- where are the initial demographics. I think the post-transplant segment is a particularly interesting one.

我們不僅研究了移植前的情況，也研究了移植後的情況，而移植後的情況經常被忽略。我們對兒科患者和成人進行了研究，研究了這種疾病中有時 C3 耗盡時的情況。有時我們並沒有研究過一切。就對疾病的影響而言，我們看到各地都做出了一致的反應。所以這意味著什麼，因為我認為你要問的是最初的人口統計在哪裡。我認為移植後的部分特別有趣。

I think it's also worth noting that within this small community of transplant nephrologists, EMPAVELI is taking on quite a pristine reputation, not just because of the data that we had in Valeant, but also because all of the recent Zero transplants, you may have seen in the news, the kidney transplants that are happening from genetically modified pigs are transplants that were either rescues with EMPAVELI or are now in all cases, as far as we know, proactively being protected with EMPAVELI. So the -- I'd say the reputation of EMPAVELI to be able to control complement within the kidney is growing steadily and something that, of course, bodes well for our launch later in this year.

我認為還值得注意的是，在這個小型的移植腎病學家社區中，EMPAVELI 享有相當高的聲譽，這不僅是因為我們在 Valeant 擁有的數據，還因為您可能在新聞中看到的所有最近的零移植，從轉基因豬身上進行的腎臟移植要么是使用 EMPAVELI 進行挽救的移植，要么現在在所有情況下，據我們所知，LILILI 的主動保護。所以——我想說，EMPAVELI 在控制腎臟補體方面的聲譽正在穩步增長，這當然對我們今年稍後推出的產品來說是一個好兆頭。

That's very helpful. Thank you.

這非常有幫助。謝謝。

Akash Tewari, Jefferies.

Akash Tewari，傑富瑞（Jefferies）。

Hi, this is Kathy on for our Akash. So on (inaudible) earnings call, they stated that docs were essentially warehousing patients and pausing their IZERVAY doses until the 24-month label update rather than sitting them to SYFOVRE? And then as such, they were expecting a bolus in March once dosing resumes.

大家好，我是 Kathy，今天為大家帶來 Akash 節目。所以在（聽不清楚）財報電話會議上，他們表示醫生基本上是將患者倉儲起來並暫停他們的 IZERVAY 劑量直到 24 個月的標籤更新，而不是讓他們等待 SYFOVRE？因此，他們預計，一旦三月恢復給藥，就會進行一次推注。

So given the IZERVAY label got updated a couple of weeks before the PDUFA with the two year data on the label, but without every other month dosing, what are you seeing in terms of SYFOVRE versus serve IZERVAY within the past few weeks? And then what should we expect regarding dynamics on SYFOVRE versus IZERVAY going forward? And then what do you think your team needs to do to change doctors perception? Thank you.

因此，鑑於 IZERVAY 標籤在 PDUFA 頒布前幾週進行了更新，標籤上有兩年的數據，但沒有每隔一個月的劑量，您在過去幾週內看到 SYFOVRE 與 IZERVAY 的使用情況如何？那麼，我們對 SYFOVRE 與 IZERVAY 未來的動態應該有何期待？那麼您認為您的團隊需要做些什麼來改變醫師的看法？謝謝。

Yes. So I think I will answer the first part, and then I will hand it over to Caroline to talk about doctor perception, which of course is very important. But I think, look, there may have been some warehousing with certain physicians with certain patients to take home very clearly here is that we are a definitive market leader and we are growing that leadership.

是的。所以我想我會回答第一部分，然後我會把它交給 Caroline 來談論醫生的看法，這當然非常重要。但我認為，看，可能與某些醫生和某些患者有一些倉儲，可以非常清楚地表明我們是明確的市場領導者，而且我們正在發展這種領導地位。

That is very clear from all of the intels that we have internally at Apellis and something that is rooted in the data that we have, right? So I think that is the key message for us. And I'll hand over to Caroline to talk about how physicians currently view the products.

從 Apellis 內部掌握的所有情報以及我們掌握的數據中可以清楚看出這一點，對嗎？所以我認為這是對我們來說的關鍵訊息。我將把時間交給卡羅琳來談談醫生目前如何看待這些產品。

Thank you, Cedric. Well, we hear a lot from our physician colleagues we just attended three major meetings, most recently the Macula Society. And physicians are very enthusiastic about our differentiated efficacy data. And our long-term data, I mean, we presented tissue saves and how much tissue that was that was over 1.5 disc of retina tissue that's (inaudible) with SYFOVRE use, and we presented long-term data, patients who've been treated with SYFOVRE for 48 months. So this is really unprecedented and this is the key driver amongst physicians. I think that in the end that physicians really speak to the scientific data and it's very meaningful for them.

謝謝你，塞德里克。嗯，我們從醫生同事那裡聽到了很多消息，我們剛剛參加了三次重要會議，最近一次是黃斑學會會議。而且醫生們對我們差異化的療效數據非常熱情。我們的長期數據是，我們展示了組織保存情況，以及使用 SYFOVRE 後保存了多少超過 1.5 個視網膜組織盤（聽不清楚），我們還展示了長期數據，即接受 SYFOVRE 治療 48 個月的患者。這確實是史無前例的，也是醫生們關注的關鍵驅動因素。我認為最終醫生確實會談論科學數據，這對他們來說非常有意義。

Okay. Understood. And then just like a super quick follow-up. It seems like -- could you provide some more color on inventory in Q4 because it seems like quarter-over-quarter sales growth was about 10% versus vol growth was about 5%, but you mentioned that your stable gross to net dynamics. Thank you.

好的。明白了。然後就像一個超級快速的後續行動。似乎——您能否提供一些有關第四季度庫存的更多信息，因為似乎季度環比銷售額增長約為 10%，而成交量增長約為 5%，但您提到了穩定的毛利與淨利動態。謝謝。

Yes. Yes. This is David. So thank you for the question. coming out in Q4. And usually, you'll see in any given quarter, at the end of the quarter, some move in regards to orders that will move inventory a little bit. We saw a little bit, of course, coming out of Q4 and sometimes you'll see a little bit more around the holidays. But it did not put us in a situation that we were out in a typical 2- to 3-week range that we have. And we may see a little bit of drawdown in the front of Q1, but -- for the most part, it was not a significant number that we would be concerned about in any way.

是的。是的。這是大衛。感謝您的提問。將於第四季推出。通常，您會看到在任何一個季度末，訂單方面都會有一些變動，從而導致庫存略有變動。當然，我們在第四季度看到了一些，有時你會在假期期間看到更多。但它並沒有讓我們陷入通常需要 2 到 3 週的情況。我們可能會在第一季初期看到一點下滑，但是，總體而言，這並不是一個值得我們擔心的重大數字。

Got it. Understood. Thank you.

知道了。明白了。謝謝。

Ellie Merle, UBS.

瑞銀的艾莉·梅爾（Ellie Merle）

Thanks for taking my question. In terms of TA, I guess, what's the latest that you're seeing in terms of patient adherence and what you're seeing in terms of any discontinuations, I guess sort of how we should be thinking about long term, what the destination rate or compliance on therapy might be?

感謝您回答我的問題。就 TA 而言，我想，您在患者依從性方面看到的最新情況是什麼？在停藥方面您看到的情況如何？我想我們應該如何考慮長期情況，治療的目標率或依從性可能是多少？

And then just a second question, in terms of your expectations for the number of samples beyond 1Q, I guess, what do you expect in terms of dynamic in 2Q on the rest of the year. You mentioned this was a temporary funding gap in the patient-assisted organizations. But just curious what you expect over the course of the year in terms of the number of samples. Thanks.

然後第二個問題，就您對第一季以後的樣本數量的預期而言，我想，您對第二季和今年剩餘時間的動態有何預期？您提到這是病患援助組織的暫時資金缺口。但我很好奇，就樣本數而言，您對全年的預期是多少。謝謝。

Yes. Thank you so much, Ellie. So first of all, as it relates to the adherence, we actually see adherence levels for SYFOVRE will be similar to what we have or what you find with anti-VEGF which is a very positive trend, considering that is kind of more viewed as an acute treatment with an immediate benefit, whereas with SYFOVRE as we all know, you make an investment in the future protection and this large amount of tissue that you can preserve if you are faithful to the product. So that is something that we have no concerns around. As it relates to the samples, I will have David answer that.

是的。非常感謝，艾莉。首先，就依從性而言，我們實際上看到 SYFOVRE 的依從性水平與我們所擁有的或您發現的抗 VEGF 的依從性水平相似，這是一個非常積極的趨勢，因為它更多地被視為一種具有直接益處的急性治療，而對於 SYFOVRE，眾所周知，您是對未來的保護進行投資，如果您可以保留大量產品，就可以保留您的組織。因此我們對此毫不擔心。至於與樣本有關的問題，我將讓大衛來回答。

Yes. So I think a couple of things. And just remember, upfront, I think it's important to remember that samples being requested and put into a patient for treatment is a sign of demand, which is very positive for us. And we're seeing the injections increase in Q1 versus Q4. So we feel good about that.

是的。所以我想到了幾點。首先要記住的是，我認為重要的是要記住，要求提供樣本並放入患者體內進行治療是需求的標誌，這對我們來說非常積極。我們發現第一季的注射量相對於第四季有所增加。因此我們對此感到很高興。

I think a couple of things. First of all, we believe this is temporary, and we anticipate that these issues that we're working on that the samples are being used in place that the commercial product will be fixed over time.

我想有幾件事。首先，我們認為這只是暫時的，我們預計，我們正在努力解決的這些問題以及商業產品使用過程中出現的問題將隨著時間的推移而解決。

We don't know what that looks like as far as timing and the funding gap and when all those things kind of come together, that Cedric mentioned, it's really -- it's in the control of the groups that manage this with patients and with physicians. So we really don't have an answer to that. But we will continue to supply samples if needed and put patients in a place where they can be treated.

我們不知道時間和資金缺口會是怎樣，也不知道當所有這些事情結合在一起時，正如塞德里克提到的，這實際上 - 它處於與患者和醫生一起管理此事的團體的控制之下。所以我們真的沒有答案。但如果需要，我們將繼續提供樣本，並將患者送到可以接受治療的地方。

Got it. Thanks.

知道了。謝謝。

Annabel Samimy, Stifel.

安娜貝爾·薩米 (Annabel Samimy)，Stifel。

Hi, thanks for taking my question. So I'm just trying to understand the competitive dynamics a little bit better for SYFOVRE. Can you help us square away comments about leadership position of greater than 60% share. But then new patients is more like 50% and then we've got competitive headwinds coming from the label expansion with the new talk about positive trends in injection growth, preferred formulary status and positive feedback that you're getting from the community around efficacy and flexibility of SYFOVRE.

你好，謝謝你回答我的問題。所以我只是想更了解 SYFOVRE 的競爭動態。您能幫我們解決關於佔有超過 60% 份額的領導地位的評論嗎？但是新患者數量卻超過了 50%，而且我們面臨著來自標籤擴展的競爭阻力，新話題涉及注射劑增長的積極趨勢、首選處方狀態以及您從社區獲得的有關 SYFOVRE 的功效和靈活性的積極反饋。

So I guess maybe you can help us really understand what that competitive headwind is that is pushing the new patient share to 50-50 because it looks like everything is sort of lining up well for SYFOVRE, but I'm not sort of able to square away why it's still 50-50 for the new patient share.

所以我想也許你可以幫助我們真正理解是什麼競爭阻力將新患者份額推到了 50-50，因為看起來一切都對 SYFOVRE 有利，但我無法解釋為什麼新患者份額仍然是 50-50。

Yes. Thank you, Annabel. I think look, -- we'll see where it ultimately will end up, of course, right? I mean we -- the direction is positive for us, right? So -- but I think most importantly, even a couple of months ago, I think we were in a competitive situation where the data or the knowledge around our competitor was, I would say, weak in the retina community.

是的。謝謝你，安娜貝爾。我想，我們會看到它最終會走向何方，當然，對吧？我的意思是——這個方向對我們來說是正面的，對吧？所以 — — 但我認為最重要的是，即使在幾個月前，我認為我們也處於一個競爭激烈的局面，我認為在視網膜社群中，我們競爭對手的數據或知識還很薄弱。

As far as it relates to what does this drug actually do? What does it do in the long run? A lot of physicians, as I mentioned, didn't know that this drug was only approved initially for a one year period. So that was a (inaudible) surprise. So I think that we are now playing in a level playing field and the level playing field, the differentiation on efficacy is incredibly robust, right, and that is being recognized by retina doctors.

就此藥物的實際作用而言？長遠來看它有什麼作用？正如我所提到的，很多醫生並不知道這種藥物最初只被批准使用一年。所以這是一個（聽不清楚）驚喜。所以我認為我們現在處於一個公平的競爭環境中，在公平的競爭環境中，療效的差異化非常明顯，對吧，這一點也得到了視網膜醫生的認可。

And that's not just on a magnitude basis, it is also on the longitudinal data. And I would say that it's a real turning point for us that we're looking forward to working from. I don't know, Caroline, if you want to add something?

這不僅基於量級，也基於縱向資料。我想說這對我們來說是一個真正的轉捩點，我們期待從這裡開始努力。我不知道，卡洛琳，你是否想補充一點？

Well, I think one of the things that really differentiates us with physicians is that every other month dosing. And we use clinical studies to guide us. And the robust data we have a heterogeneous broad patients that were studied all show demonstrate the efficacy into year four with every other month dosing, which will just increase the convenience and help patients stay compliant. So I mean, physicians continually come up to me, grateful for what we're presenting and show that this long term and every other month dosing, it speaks to their patient population.

嗯，我認為我們與醫生的真正區別之一就是每隔一個月服藥。我們用臨床研究來指導我們。我們擁有來自廣泛異質性患者的可靠研究數據，所有數據均表明，每隔一個月服藥一次的治療在第四年仍有效，這將增加便利性並幫助患者保持依從性。所以我的意思是，醫生們不斷地來找我，感謝我們所展示的方法，並表明這種長期和每隔一個月的用藥對他們的患者群體有好處。

Okay. Great. And if I could just ask a question on C3G, MPGN launch. What are your expectations there? You're not -- (inaudible) clearly got some out a little bit earlier, but you did mention that physicians were a little bit more focused on -- are a lot more focused on efficacy. But I'm curious the level of urgency patients have to get on treatment. And so what can we expect for, I guess, an early launch trajectory for that product?

好的。偉大的。我可以問一個關於 C3G、MPGN 發布的問題嗎？您對此有何期望？您不是 — — （聽不清楚）顯然早些時候就提到了一些，但您確實提到醫生更加關注 — — 更加關注療效。但我很好奇患者接受治療的緊迫程度。那麼，我們對該產品的早期發布軌跡有何期待呢？

Yes. Thank you, Annabel. I think the key thing is that we -- we see the demand in the request that we already get for compassion use and expanded use access, right. So demand is very important. Remember, these are younger patients, about half of whom over a 10-year period, which is not a lot when you're 20 or 30, 50% is the chance of losing their kidneys. So the need is incredibly high. And again, I want to emphasize that based on the data that we have, we will probably be competing probably only for about 20% of that overall bucket of patients. So a really important opportunity for us and for patients.

是的。謝謝你，安娜貝爾。我認為關鍵在於我們——我們在已經收到的請求中看到了對同情使用和擴大使用管道的需求，對吧。所以需求非常重要。請記住，這些都是較年輕的患者，其中約一半在 10 年內失去腎臟，這對於 20 或 30 歲的年輕人來說並不多，有 50% 的機會失去腎臟。因此，需求非常高。我想再次強調，根據我們掌握的數據，我們可能只能爭奪整體患者群體的 20% 左右。這對我們和病人來說都是一個非常重要的機會。

Okay. Great. Thank you.

好的。偉大的。謝謝。

Douglas Tsao, H.C. Wainwright.

曹國偉，H.C.溫賴特。

Hi, good morning. Thanks for taking my question. First question I had was in terms of the (inaudible) SYFOVRE product, Cedric. I know in the past, spoken about SYFOVRE having a very powerful effect on preservation of photoreceptors and less so on RPE cells. And so I'm just curious, with this approach, is this sort of what you're specifically targeting by going after the chlorate, which isn't which is sort of a case to the RPE as well?

嗨，早安。感謝您回答我的問題。我的第一個問題是關於（聽不清楚）SYFOVRE 產品，塞德里克。我知道過去曾談到 SYFOVRE 對光感受器的保存具有非常強大的作用，而對 RPE 細胞的作用則較小。所以我很好奇，透過這種方法，您透過追蹤氯酸鹽所專門針對的是否也是 RPE 的情況？

Well, [tech], I'm very impressed with that question, but you are correct. This is -- so the impact that SYFOVRE has on the photoreceptors is near perfect. What about 100% when you look in the first six months. I mean it's an incredibly robust impact on those receptors.

嗯，[技術]，我對這個問題印象深刻，但你是對的。這是——因此 SYFOVRE 對光感受器的影響近乎完美。如果你看一下前六個月的情況，那麼 100% 怎​​麼樣？我的意思是它對這些受體有非常強烈的影響。

The RPE cells are the ones that continue today, of course, meaningfully slow down. And then the question that we're trying to answer here is since if we -- on the choroidal side, right, on the back of the eye, if we can lower C3 levels, will we be able to impact the RPE cells in a way that is similar to the full receptors. So excellent question, and the answer is yes.

當然，RPE 細胞至今仍在持續生長，但速度已明顯減慢。然後，我們在這裡嘗試回答的問題是，如果我們 —— 在脈絡膜側，對吧，在眼球後部，如果我們可以降低 C3 水平，我們是否能夠以類似於完整受體的方式影響 RPE 細胞。這個問題問得非常好，答案是肯定的。

Okay. Great. And just a quick follow-up for David. Just I'm curious to the extent that you anticipate seeing an impact on the Medicare redesign for this year or if you can sort of quantify it at this point?

好的。偉大的。這只是對 David 的簡短跟進。我只是很好奇，您預計今年的醫療保險重新設計將受到多大影響，或者您可以量化它？

Thank you for the question. I think quantifying that is challenging for us, and I would hate to take a guess at it. So it's something we're looking at. We've got a whole team, of course, that manages all the things that we do with payers and especially in our space with CMS. But I don't think I can quantify that at least at this time.

感謝您的提問。我認為量化這一點對我們來說是一個挑戰，而且我不願意對此進行猜測。這是我們正在關注的事情。當然，我們有一個完整的團隊，負責管理我們與付款人有關的所有事務，特別是在 CMS 領域。但我認為至少目前我還無法量化這一點。

Okay. Great. Thank you so much.

好的。偉大的。太感謝了。

Joseph Stringer, Needham & Company.

約瑟夫·斯特林格，尼德漢姆公司。

Hi, good morning. Thank you for taking my question. Two from us. Just wanted to get your updated comment, -- on any on the switching dynamics between Sobi and IZERVAY. And secondly, I know prior question asked about adherence rates, but just curious what about compliance rates for SYFOVRE, for example, patients missing or skipping injection. How does that look? Or how has that changed over time? Thank you.

嗨，早安。感謝您回答我的問題。我們有兩個。只是想獲得您關於 Sobi 和 IZERVAY 之間的切換動態的最新評論。其次，我知道之前的問題是關於依從率，但我只是好奇 SYFOVRE 的依從率如何，例如患者漏注射或跳過注射。看起來怎麼樣？或是隨著時間的推移發生了怎樣的變化？謝謝。

So this is David. Thank you for the question. A couple of things. I think Cedric and Caroline touched on already some of the compliance where we fall with SYFOVRE and it's about in the same range as anti-VEGF. So -- and actually, I feel good about that because for us to be in the GA treatment area with something that's that compliant, I think is very positive because it is a disease of is definitely slower than Wet AMD.

這就是大衛。感謝您的提問。有幾件事。我認為 Cedric 和 Caroline 已經談到了我們對 SYFOVRE 的一些遵守情況，它與抗 VEGF 處於同一範圍。所以 — — 實際上，我對此感到很高興，因為對於我們來說，在 GA 治療領域有如此合規的治療，我認為這是非常積極的，因為它是一種比濕性 AMD 進展慢的疾病。

As far as the -- as far as the question on the dynamics of switching, so we look at this on a regular basis. I will tell you that we've had a number of weeks, especially during the CRL period that they had for the competitive product that we saw a number of switches. And I still think we're seeing that today in the first part of the front end of Q1. And the good thing is, and I think what's driving my thinking around that is the fact that we are seeing an increase in injections in Q1 versus Q4. And I think that we're in a good place to see growth overall in 2025.

至於──關於轉換動態的問題，我們會定期檢視這個問題。我會告訴你，我們已經有好幾個星期了，特別是在他們為競爭產品製定的 CRL 期間，我們看到了許多轉變。我仍然認為我們今天在第一季前端看到了這一點。好消息是，我認為促使我這樣想的原因是我們看到第一季的注射量相對於第四季有所增加。我認為，到 2025 年，我們有望實現整體成長。

Lachlan Hanbury-Brown, William Blair.

拉克蘭·漢伯里·布朗，威廉·布萊爾。

Hi, guys. Thanks for taking my question. I wanted to ask more about the efforts that you've made to get doctors off the sideline. You said that the sort of shift towards the efficacy-focused messaging is resonating well with physicians. But I'm wondering if you can sort of translate that into any changes of actual prescribing behaviors or new prescribers?

嗨，大家好。感謝您回答我的問題。我想進一步詢問您為讓醫生擺脫困境所做的努力。您說過，這種以療效為重點的傳遞方式的轉變引起了醫生的強烈共鳴。但我想知道您是否可以將其轉化為實際開藥行為或新開藥人員的變化？

Yes. So that is what we are seeing. Thank you for that question. I think what is gratifying after three years of launch now is that the data becomes very clear, right? We have the extension study, the data becomes much more concise to communicate. And the main message at Macula Society, which is one that I think really resonates the most is that if you are on four years of treatment with SYFOVRE, you can have up to 3 square millimetres of retina preserved, right?

是的。這就是我們所看到的。感謝您的提問。我覺得現在經過三年的推出，值得欣慰的是數據變得非常清楚了，對吧？我們進行了擴展研究，數據變得更簡潔，也更容易溝通。黃斑部協會的主要訊息，也是我認為最能引起共鳴的訊息是，如果您接受 SYFOVRE 治療四年，您可以保留多達 3 平方毫米的視網膜，對嗎？

And three square millimeters of retina is one in the health is areas, a huge amount of real estate in the back of the (inaudible). That is many tell physicians that resonate incredibly well. That is the reality of this drug and one that we can now really use moving forward. The safety situation is very stable and efficacy is becoming a brand focus.

視網膜的三平方毫米是健康區域之一，視網膜後部有巨大的空間（聽不清楚）。許多告訴醫生這引起了非常好的共鳴。這就是這種藥物的現實情況，也是我們現在可以真正使用它來向前邁進的。安全狀況非常穩定，功效正成為品牌關注的焦點。

Got it. Thanks. And a follow-up, if I may, sort of following up on your [got] earlier question on patent life for EMPAVELI. Curious if you can give any color on what you had assumed for IRA price negotiations when you were doing the sort of business cases for FSGS and DGF, I realize there's probably still more questions and answers there, but just would be great to get your thoughts on sort of what you'd assumed?

知道了。謝謝。如果可以的話，我想問一下您之前關於 EMPAVELI 專利期限的問題。我很好奇，當您為 FSGS 和 DGF 做商業案例時，您是否可以說明一下您對 IRA 價格談判的假設，我意識到可能還有更多的問題和答案，但如果您能聽聽您對這些假設的看法就更好了？

Yes. Thank you so much. So these are -- look, we did a thorough analysis after the readout of Valiant of indicate me based on the premise that we have clearly exquisite target engagements in the glomerulus. And we did the usual work that you do in that situation, the competitive analysis, the biology, what can we do with the patent lab of the drug, and that is where these two the CCC emerge. So much more will follow, but we're excited about these indications and when we get the full indications.

是的。太感謝了。所以這些是——你看，在Valiant的讀數之後，我們做了一個徹底的分析，這個分析是基於我們在腎小球中擁有明顯精妙的目標交戰的前提。我們做了在這種情況下通常要做的工作，競爭分析、生物學，我們可以利用藥物專利實驗室做些什麼，這就是這兩個 CCC 出現的地方。隨後還會有更多消息，但我們對這些跡像以及獲得全部跡象感到很興奮。

Ryan Deschner, Raymond James.

瑞安‧德施納、雷蒙‧詹姆斯。

Hi, good morning. Thanks for the question. Have your expectations for gross to net in 2025 and a steady state evolved at all in the last few months? And can you give us any more detail on what you're expecting to see in terms of timing and duration of the impact of the new DTC campaign on sales in 2025 and beyond based on what you saw in the prior campaign. Thank you.

嗨，早安。謝謝你的提問。在過去的幾個月裡，您對 2025 年毛利潤與淨利潤的預期以及穩定狀態是否有所變化？根據您在先前的活動中看到的情況，您能否向我們詳細介紹您預計新的 DTC 活動對 2025 年及以後的銷售的影響的時間和持續時間。謝謝。

Yes. Thank you very much for the question. I'll take the gross to net piece and then hand it over to David for the impact of the DTC. So the simple answer is no. Our view on gross event hasn't changed at all. At the end of the third quarter, we did guide to low to mid-20s throughout the course of 2025, and that remains the same. And David?

是的。非常感謝您的提問。我會將毛利減去淨利，然後將其交給大衛，以評估 DTC 的影響。因此簡單的答案是否定的。我們對嚴重事件的看法一點都沒有改變。在第三季末，我們確實預測到 2025 年全年成長率將達到 20% 左右，而且這項預測仍然保持不變。還有大衛？

Yes. Thank you, Tim. So I appreciate the question on DTC. It's a little early. We started running that commercial on television with Henry Wikler in mid-January. But I can give you one piece of information that happens that will give you an indicator of some of the early impact that we can see.

是的。謝謝你，提姆。因此，我很感謝有關 DTC 的問題。有點早。我們從一月中旬開始與亨利·威克勒一起在電視上播放這個廣告。但我可以提供一條訊息，讓你們了解我們能夠看到的一些早期影響。

We did have the commercial run during the Saturday Night Live 50th anniversary special. We had about 15 million views on the commercial, which was attributed to driving about 3,000 visits on our website, at that time. So we can see things like that early. It's going to take time for us to see the total impact throughout the next several months.

我們確實在周六夜現場 50 週年特別節目期間播放了廣告。當時，這則廣告的觀看次數約為 1500 萬次，為我們的網站帶來了約 3000 次訪問。因此我們可以提前看到這樣的事情。我們需要花一些時間才能看到未來幾個月的整體影響。

Excellent. Thank you very much.

出色的。非常感謝。

Derek Archila, Wells Fargo.

富國銀行的德里克‧阿奇拉 (Derek Archila)。

Hey, good morning, and thanks for taking my question. Maybe just two for Tim. I guess, how should we think about OpEx growth in 2025 relative to '24? Is there going to be a lot of growth coming from some of the R&D initiatives that you guys talked about. And just based on some of the seasonal factors in 1Q and the sampling, I guess how should we be thinking about gross margin trends to '25? Thanks.

嘿，早上好，感謝您回答我的問題。對蒂姆來說可能只有兩個。我想，我們該如何看待 2025 年相對於 24 年的營運支出成長？你們談到的一些研發計劃是否會帶來很大的成長？僅基於第一季的一些季節性因素和抽樣，我想我們應該如何考慮到 25 年的毛利率趨勢？謝謝。

Sure. So from the perspective of OpEx versus 2024, as we said in our prepared remarks that we expect those to be more or less the same. I think that's probably the case when you think about what we've -- some cost savings from our European infrastructure some of which we scaled down. That will be offset by some R&D expenditure that gets increased.

當然。因此，從 2024 年的營運支出角度來看，正如我們在準備好的評論中所說的那樣，我們預計它們會大致相同。我想，如果你想想我們所做的事情，情況可能就是這樣——我們從歐洲基礎設施中節省了一些成本，其中一些是我們縮減的。這將被增加的部分研發支出所抵銷。

And then from the gross margin perspective, we don't guide on that. There are -- there's a lot that goes into gross margin that sort of moves around. But from a sampling perspective, I think we gave you everything we could from the perspective of color on how we project that.

然後從毛利率的角度來看，我們不會對此做出指導。有很多因素都會影響毛利率，而且這種影響是不斷變化的。但是從採樣的角度來看，我認為我們從顏色的角度為您提供了我們可以投射的一切。

We really don't have any visibility. But we do know what we did talk about is that we see an approximately 5000 vial estimated increase of samples in this quarter. And so doing the math on that, you can kind of get to a reasonable idea of what our revenue is per file.

我們確實沒有任何可見性。但我們確實知道，我們所談論的是，我們看到本季樣品數量估計增加了約 5000 瓶。透過計算，你就能大致了解每個文件的收入是多少。

You can understand what that would be. And frankly, that's the piece that we can right now kind of get into our gross margin impact in the first quarter, at least as an estimate. Beyond that, we really have no visibility, unfortunately.

您可以理解那會是什麼。坦白說，這是我們現在能夠得到的對第一季毛利率影響的部分，至少是一個估計值。不幸的是，除此之外，我們真的什麼也看不見。

Got it. Thank you.

知道了。謝謝。

And I would now like to turn the call back to Cedric Francois for closing remarks.

現在我想請塞德里克‧弗朗索瓦 (Cedric Francois) 作結束語。

Thank you so much, and thank you, everyone, for joining us this morning. If you have any follow-up questions, please feel free to reach out to Meredith. Thank you so much.

非常感謝，也感謝大家今天早上加入我們。如果您有任何後續問題，請隨時聯絡 Meredith。太感謝了。

And this concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。